公开(公告)号：US09611471B2

公开(公告)日：2017-04-04

申请号：US13814203

申请日：2011-08-04

申请人： Wilhelmina M. C. van Roon-Mom ,  Melvin Maurice Evers ,  Barry Antonius Pepers ,  Annemieke Aartsma-Rus ,  Garrit-Jan Boudewijn Van Ommen

发明人： Wilhelmina M. C. van Roon-Mom ,  Melvin Maurice Evers ,  Barry Antonius Pepers ,  Annemieke Aartsma-Rus ,  Garrit-Jan Boudewijn Van Ommen

IPC分类号： C12N15/113 ,  C12N15/11

CPC分类号： C12N15/113 ,  C12N15/111 ,  C12N2310/11 ,  C12N2310/315 ,  C12N2310/321 ,  C12N2310/346 ,  C12N2320/33 ,  C12N2310/3521

摘要： Described are means and methods for removing a proteolytic cleavage site from a protein, the method comprising providing a cell that expresses pre-mRNA encoding the protein with an anti-sense oligonucleotide that induces skipping of the exonic sequence that encodes the proteolytic cleavage site, and allowing translation of mRNA produced from the pre-mRNA.

公开(公告)号：US20110263682A1

公开(公告)日：2011-10-27

申请号：US13094571

申请日：2011-04-26

申请人： Josephus Johannes De Kimpe ,  Gerardus Johannes Platenburg ,  Judith Christina Theodora Van Deutekom ,  Annemieke Aartsma-Rus ,  Garrit-Jan Boudewijn Van Ommen

发明人： Josephus Johannes De Kimpe ,  Gerardus Johannes Platenburg ,  Judith Christina Theodora Van Deutekom ,  Annemieke Aartsma-Rus ,  Garrit-Jan Boudewijn Van Ommen

IPC分类号： A61K31/7088 ,  C12N5/071 ,  C12N15/85 ,  C07H21/02 ,  A61P21/00

CPC分类号： C12N15/113 ,  A61K31/56 ,  A61K31/57 ,  A61K31/573 ,  A61K31/58 ,  A61K31/7088 ,  A61K38/1719 ,  A61K45/06 ,  A61K48/00 ,  C12N2310/11 ,  C12N2310/111 ,  C12N2310/31 ,  C12N2310/313 ,  C12N2310/314 ,  C12N2310/315 ,  C12N2310/3181 ,  C12N2310/321 ,  C12N2310/3231 ,  C12N2310/3233 ,  C12N2310/346 ,  C12N2320/31 ,  C12N2320/33 ,  A61K2300/00

摘要： The invention relates a method wherein a molecule is used for inducing and/or promoting skipping of at least one of exon 43, exon 46, exons 50-53 of the DMD pre-mRNA in a patient, preferably in an isolated cell of a patient, the method comprising providing said cell and/or said patient with a molecule. The invention also relates to said molecule as such.

摘要翻译： 本发明涉及一种方法，其中分子用于诱导和/或促进患者，优选在患者的分离的细胞中的DMD前体mRNA的外显子43，外显子46，外显子46-5，外显子50-53中的至少一个的跳跃 所述方法包括向所述细胞和/或所述患者提供分子。 本发明也涉及所述分子。

公开(公告)号：US08802645B2

公开(公告)日：2014-08-12

申请号：US13529640

申请日：2012-06-21

申请人： Garrit-Jan Boudewijn Van Ommen ,  Annemieke Aartsma-Rus ,  Judith Christina Theodora Van Deutekom ,  Josephus Johannes De Kimpe ,  Joseph Stephan Verbeek ,  Aliye Seda Ylmaz-Elis

发明人： Garrit-Jan Boudewijn Van Ommen ,  Annemieke Aartsma-Rus ,  Judith Christina Theodora Van Deutekom ,  Josephus Johannes De Kimpe ,  Joseph Stephan Verbeek ,  Aliye Seda Ylmaz-Elis

IPC分类号： A61K31/70 ,  C07H21/02 ,  C07H21/04 ,  C12N15/113 ,  C12N15/11 ,  C12Q1/68

CPC分类号： C12N15/113 ,  A61K31/7115 ,  A61K31/712 ,  C12N15/111 ,  C12N15/1138 ,  C12N2310/11 ,  C12N2320/30 ,  C12N2320/33

摘要： The invention provides two types of oligonucleotides for treating an inflammatory disorder: an oligonucleotide which is able of altering the splicing of a pre-mRNA encoding a C5 in order to decrease the amount of a C5a and an oligonucleotide which is able of altering the splicing of a pre-mRNA encoding a IL-1RAcP in order to increase the amount of a soluble IL-1RAcP. The invention further provides the use of said oligonucleotides for preventing or treating an inflammatory disorder.

摘要翻译： 本发明提供两种用于治疗炎性病症的寡核苷酸：能够改变编码C5的前mRNA的剪接的寡核苷酸，以减少C5a的量和能够改变剪接的寡核苷酸 编码IL-1RAcP的前mRNA是为了增加可溶性IL-1RAcP的量。 本发明还提供了所述寡核苷酸用于预防或治疗炎症性疾病的用途。

公开(公告)号：US20120059042A1

公开(公告)日：2012-03-08

申请号：US12992218

申请日：2010-11-11

申请人： Gerard Johannes Platenburg ,  Josephus Johannes de Kimpe ,  Judith Christina Theodora van Deutekom ,  Garrit-Jan Boudewijn van Ommen ,  Annemieke Aartsma-Rus

发明人： Gerard Johannes Platenburg ,  Josephus Johannes de Kimpe ,  Judith Christina Theodora van Deutekom ,  Garrit-Jan Boudewijn van Ommen ,  Annemieke Aartsma-Rus

IPC分类号： A61K31/7105 ,  A61P21/00 ,  C12N5/10 ,  C07H21/02 ,  C12N15/63

CPC分类号： C12N15/113 ,  A61K48/00 ,  C12N2310/11 ,  C12N2310/111 ,  C12N2310/314 ,  C12N2310/315 ,  C12N2310/321 ,  C12N2310/3233 ,  C12N2310/346 ,  C12N2310/3513 ,  C12N2310/3517 ,  C12N2320/33 ,  C12N2310/3521

摘要： The invention relates to a nucleic acid molecule that binds and/or is complementary to the nucleotide molecule having sequence 5′-GUGGCUAACAGAAGCU (SEQ ID NO 1) and to its use in a method for inducing skipping of exon 44 of the DMD gene in a DMD patient.

摘要翻译： 本发明涉及与具有序列5'-GUGGCUAACAGAAGCU（SEQ ID NO 1）的核苷酸分子结合和/或互补的核酸分子，并且其用于诱导在DMD基因的外显子44中跳跃的方法 DMD患者。

公开(公告)号：US20110294753A1

公开(公告)日：2011-12-01

申请号：US12767702

申请日：2010-04-26

申请人： Josephus Johannes De Kimpe ,  Gerard Johannes Platenburg ,  Judith Christina Theodora Van Deutekom ,  Annemieke Aartsma-Rus ,  Garrit-Jan Boudewijn Van Ommen

发明人： Josephus Johannes De Kimpe ,  Gerard Johannes Platenburg ,  Judith Christina Theodora Van Deutekom ,  Annemieke Aartsma-Rus ,  Garrit-Jan Boudewijn Van Ommen

IPC分类号： A61K31/7105 ,  C12N5/071 ,  A61P29/00 ,  A61K31/4245 ,  A61P21/00 ,  A61K31/7036 ,  A61K31/712

CPC分类号： C12N15/113 ,  A61K31/56 ,  A61K31/57 ,  A61K31/573 ,  A61K31/58 ,  A61K31/7088 ,  A61K38/1719 ,  A61K45/06 ,  A61K48/00 ,  C12N2310/11 ,  C12N2310/111 ,  C12N2310/31 ,  C12N2310/313 ,  C12N2310/314 ,  C12N2310/315 ,  C12N2310/3181 ,  C12N2310/321 ,  C12N2310/3231 ,  C12N2310/3233 ,  C12N2310/346 ,  C12N2320/31 ,  C12N2320/33 ,  A61K2300/00

摘要： The invention provides means and methods for alleviating one or more symptom(s) of Duchenne Muscular Dystrophy and/or Becker Muscular Dystrophy. Therapies using compounds for providing patients with functional muscle proteins are combined with at least one adjunct compound for reducing inflammation, preferably for reducing muscle tissue inflammation, and/or at least one adjunct compound for improving muscle fiber function, integrity and/or survival.

摘要翻译： 本发明提供了减轻Duchenne肌营养不良症和/或Becker肌营养不良症的一种或多种症状的方法和方法。 使用化合物提供功能性肌肉蛋白的患者的治疗与至少一种辅助化合物合并，用于减少炎症，优选减少肌肉组织炎症，和/或至少一种辅助化合物，用于改善肌肉纤维功能，完整性和/或存活。

公开(公告)号：US09243245B2

公开(公告)日：2016-01-26

申请号：US12767702

申请日：2010-04-26

申请人： Josephus Johannes De Kimpe ,  Gerard Johannes Platenburg ,  Judith Christina Theodora Van Deutekom ,  Annemieke Aartsma-Rus ,  Garrit-Jan Boudewijn Van Ommen

发明人： Josephus Johannes De Kimpe ,  Gerard Johannes Platenburg ,  Judith Christina Theodora Van Deutekom ,  Annemieke Aartsma-Rus ,  Garrit-Jan Boudewijn Van Ommen

IPC分类号： A61K48/00 ,  C07H21/02 ,  C07H21/04 ,  A01N45/00 ,  C12N15/113 ,  A61K31/56 ,  A61K31/57 ,  A61K38/17 ,  A61K31/7088 ,  A61K45/06

CPC分类号： C12N15/113 ,  A61K31/56 ,  A61K31/57 ,  A61K31/573 ,  A61K31/58 ,  A61K31/7088 ,  A61K38/1719 ,  A61K45/06 ,  A61K48/00 ,  C12N2310/11 ,  C12N2310/111 ,  C12N2310/31 ,  C12N2310/313 ,  C12N2310/314 ,  C12N2310/315 ,  C12N2310/3181 ,  C12N2310/321 ,  C12N2310/3231 ,  C12N2310/3233 ,  C12N2310/346 ,  C12N2320/31 ,  C12N2320/33 ,  A61K2300/00

摘要： The invention provides means and methods for alleviating one or more symptom(s) of Duchenne Muscular Dystrophy and/or Becker Muscular Dystrophy. Therapies using compounds for providing patients with functional muscle proteins are combined with at least one adjunct compound for reducing inflammation, preferably for reducing muscle tissue inflammation, and/or at least one adjunct compound for improving muscle fiber function, integrity and/or survival.

摘要翻译： 本发明提供了减轻Duchenne肌营养不良症和/或Becker肌营养不良症的一种或多种症状的方法和方法。 使用化合物提供功能性肌肉蛋白的患者的治疗与至少一种辅助化合物合并，用于减少炎症，优选减少肌肉组织炎症，和/或至少一种辅助化合物，用于改善肌肉纤维功能，完整性和/或存活。

公开(公告)号：US20120022134A1

公开(公告)日：2012-01-26

申请号：US13094548

申请日：2011-04-26

申请人： JOSEPHUS JOHANNES DE KIMPE ,  GERARDUS JOHANNES PLATENBURG ,  JUDITH CHRISTINA THEODORA VAN DEUTEKOM ,  ANNEMIEKE AARTSMA-RUS ,  GARRIT-JAN BOUDEWIJN VAN OMMEN

发明人： JOSEPHUS JOHANNES DE KIMPE ,  GERARDUS JOHANNES PLATENBURG ,  JUDITH CHRISTINA THEODORA VAN DEUTEKOM ,  ANNEMIEKE AARTSMA-RUS ,  GARRIT-JAN BOUDEWIJN VAN OMMEN

IPC分类号： A61K31/7088 ,  C12N15/63 ,  A61P21/00 ,  C12N15/113

CPC分类号： C12N15/113 ,  A61K31/56 ,  A61K31/57 ,  A61K31/573 ,  A61K31/58 ,  A61K31/7088 ,  A61K38/1719 ,  A61K45/06 ,  A61K48/00 ,  C12N2310/11 ,  C12N2310/111 ,  C12N2310/31 ,  C12N2310/313 ,  C12N2310/314 ,  C12N2310/315 ,  C12N2310/3181 ,  C12N2310/321 ,  C12N2310/3231 ,  C12N2310/3233 ,  C12N2310/346 ,  C12N2320/31 ,  C12N2320/33 ,  A61K2300/00

摘要： The invention relates to a method for inducing or promoting skipping of exon 45 of DMD pre-mRNA in a Duchenne Muscular Dystrophy patient, preferably in an isolated (muscle) cell, the method comprising providing said cell with a molecule that binds to a continuous stretch of at least 21 nucleotides within said exon. The invention further relates to such molecule used in said method.

摘要翻译： 本发明涉及一种用于诱导或促进在Duchenne肌营养不良患者（优选在分离的（肌肉））细胞中跳跃DMD前体mRNA外显子45的方法，该方法包括向所述细胞提供结合连续伸展的分子 在所述外显子中至少21个核苷酸。 本发明还涉及用于所述方法的这种分子。

公开(公告)号：US20100125099A1

公开(公告)日：2010-05-20

申请号：US12297251

申请日：2007-04-20

申请人： Peter Abraham Christiaan 't Hoen ,  Petronella Johanna Elisabeth Sterrenburg ,  Johannes Theodorus den Dunnen ,  Garrit Jan Boudewijn van Ommen

发明人： Peter Abraham Christiaan 't Hoen ,  Petronella Johanna Elisabeth Sterrenburg ,  Johannes Theodorus den Dunnen ,  Garrit Jan Boudewijn van Ommen

IPC分类号： A61K31/711 ,  C07H21/02 ,  C12N5/071 ,  C12Q1/68 ,  A61P25/28 ,  A61P21/00

CPC分类号： A61K38/185 ,  C12N5/0658 ,  C12N15/113 ,  C12N15/1136 ,  C12N2310/11 ,  C12N2310/315 ,  C12N2310/321 ,  C12N2310/346 ,  C12N2320/33 ,  C12N2501/155 ,  C12N2502/1335 ,  C12N2510/00 ,  C12N2310/3521

摘要： The present invention provides means and methods for alleviating genetic disease. A genetic defect that has a phenotype in differentiated cells can lead to defects in precursor cells thereof. These so-called secondary defects contribute to the overall disease of the individual. In the present invention, genetic intervention with the aim to alleviate symptoms of genetic disease is directed toward the primary genetic defect in the differentiated cell and the secondary defect in the precursor cell.

摘要翻译： 本发明提供了减轻遗传性疾病的方法和方法。 在分化细胞中具有表型的遗传缺陷可导致其前体细胞中的缺陷。 这些所谓的二次缺陷有助于个体的整体疾病。 在本发明中，旨在减轻遗传性疾病症状的遗传干预针对分化细胞中的主要遗传缺陷和前体细胞中的次要缺陷。

公开(公告)号：US20090228998A1

公开(公告)日：2009-09-10

申请号：US12383897

申请日：2009-03-30

申请人： Garrit-Jan Boudewijn van Ommen ,  Judith Christina, T. van Deutekom ,  Johannes Theodorus den Dunnen

发明人： Garrit-Jan Boudewijn van Ommen ,  Judith Christina, T. van Deutekom ,  Johannes Theodorus den Dunnen

IPC分类号： A01K67/027 ,  C12N15/87 ,  C12Q1/68 ,  C12N15/63 ,  A61K31/7088 ,  C07H21/02

CPC分类号： C12N15/11 ,  A01K2267/03 ,  A61K9/127 ,  A61K31/7088 ,  A61K48/00 ,  A61K48/005 ,  C12N15/113 ,  C12N15/86 ,  C12N2310/11 ,  C12N2310/315 ,  C12N2310/321 ,  C12N2310/346 ,  C12N2320/33 ,  C12N2750/14142 ,  C12N2310/3521

摘要： The present invention provides a method for at least in part decreasing the production of an aberrant protein in a cell, the cell comprising pre-mRNA comprising exons coding for the protein, by inducing so-called exon skipping in the cell. Exon-skipping results in mature mRNA that does not contain the skipped exon, which leads to an altered product of the exon codes for amino acids. Exon skipping is performed by providing a cell with an agent capable of specifically inhibiting an exon inclusion signal, for instance, an exon recognition sequence, of the exon. The exon inclusion signal can be interfered with by a nucleic acid comprising complementarity to a part of the exon. The nucleic acid, which is also herewith provided, can be used for the preparation of a medicament, for instance, for the treatment of an inherited disease.

摘要翻译： 本发明提供了至少部分降低细胞中异常蛋白质产生的方法，所述方法包括通过在细胞中诱导所谓的外显子跳跃而包含编码蛋白质的外显子的前mRNA的细胞。 外显子跳跃导致不含跳过的外显子的成熟mRNA，这导致氨基酸的外显子代码的改变的产物。 通过向细胞提供能够特异性抑制外显子包含信号（例如外显子识别序列）的外显子进行外显子跳跃。 外显子包含信号可能受到与外显子的一部分互补的核酸的干扰。 也提供了核酸可用于制备药物，例如用于治疗遗传性疾病。

公开(公告)号：US06733966B1

公开(公告)日：2004-05-11

申请号：US09445174

申请日：2000-04-24

申请人： Garrit-Jan Boudewijn van Ommen ,  Anne Petrij-Bos ,  Egbert Bakker ,  Peter Devilee

发明人： Garrit-Jan Boudewijn van Ommen ,  Anne Petrij-Bos ,  Egbert Bakker ,  Peter Devilee

IPC分类号： C12Q168

CPC分类号： C12Q1/6827 ,  C12Q1/6886 ,  C12Q2600/172

摘要： The present invention relates generally to the field of human genetics, and more specifically to the detection of a specific type of germline mutations in the BRCA1 gene, which will predispose to breast and ovarian cancer. In addition, the invention relates to the molecular genetic mechanism that may have mediated the genesis of these mutations, in particular the role of Alu repetitive DNA elements present in the intronic regions of BRCA1. The invention further relates to somatic mutations of this type in the BRCA1 gene in human breast and ovarian cancer, and their use in the diagnosis and prognosis of human breast and ovarian cancer. The invention more particularly relates to the screening of this type of BRCA1 mutations in human genomic DNA, which are useful for the diagnosis of inherited predisposition to breast and ovarian cancer.

摘要翻译： 本发明一般涉及人类遗传学领域，更具体地涉及BRCA1基因特异性种类突变的检测，其将易于乳腺癌和卵巢癌。 此外，本发明涉及可能介导这些突变的起源的分子遗传机制，特别是存在于BRCA1的内含子区域中的Alu重复DNA元件的作用。 本发明还涉及人乳腺癌和卵巢癌中BRCA1基因中这种类型的体细胞突变及其在人乳腺癌和卵巢癌诊断和预后中的应用。 本发明更具体地涉及在人类基因组DNA中筛选这种类型的BRCA1突变，其可用于诊断对乳腺癌和卵巢癌的遗传倾向。